Icodextrin Effects on Glucose Transporter Activation and Mediators of Fibrosis

NCT02133313 | Completed

• 1 other identifier: ICO-X140206005
• Study Type: observational
• Target: 49
• Locations: 1 country
• Sites: 1

Brief Summary

The time on peritoneal dialysis may be limited for a significant number of patients that use this modality of renal replacement therapy due to the inability of the peritoneal membrane to clear solutes or achieve adequate ultrafiltration, termed peritoneal membrane failure (PMF). This can be devastating for patients who have become accustomed to the quality of life provided by peritoneal dialysis and who otherwise have done well on this therapy. There is clinical evidence suggesting that icodextrin preserves the peritoneal membrane transport characteristics which may be linked to reduced cumulative glucose exposure of the peritoneal mesothelial cells. Theories to explain the role of dextrose in PMF have focused for the most part on the high intracellular concentrations of glucose without consideration to the potential pathogenic role of the glucose transporters which allow glucose entry into the cell. Experimental evidence in non-mesothelial cell lines indicate that some cellular processes that occur under high glucose conditions may not be related to intracellular glucose metabolism but to the type of glucose transporter allowing glucose entry. 3,4 However, little is known about these glucose transporters in peritoneal mesothelial cells and their potential role in the development of PMF. We hypothesize the following

• The presence of Sodium Glucose Co-transporter (SGLT1) on peritoneal mesothelial cells plays a role in PMF under hyperglycemic conditions.
• Regulation of pro-fibrotic mediators such as reactive oxidative species,transforming growth factor β, and vascular endothelial growth factor are modulated by SGLT1 activation by glucose rather than glucose metabolism or concentration.
• Icodextrin does not activate the SGLT1 transporter establishing a mechanism that may explain the beneficial effects of icodextrin on peritoneal membrane transport.

Conditions

End Stage Renal Disease

Keywords

Peritoneal Dialysis; Peritoneal Fibrosis; Glucose Transporters

Outcome Measures

Primary Outcomes (1)

• Change in glucose transporter expression on peritoneal mesothelial cells

  baseline to 3 years

Study Arms (1)

Peritoneal Dialysis Patients

Patients on Peritoneal Dialysis

Eligibility Criteria

• Age: 19 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

All patients over the age of 19 on Peritoneal Dialysis at the University of Alabama at Birmingham

You may qualify if:

• years of age or older
• On Peritoneal Dialysis

You may not qualify if:

• none

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• Baxter Healthcare Corporation: collaborator

Study Sites (1)

University of Alabama at Birmingham Home Dialysis Unit (Red Mountain Home Dialysis)

Birmingham, Alabama, 35294, United States

Location

Related Publications (6)

• Davies SJ, Phillips L, Naish PF, Russell GI. Peritoneal glucose exposure and changes in membrane solute transport with time on peritoneal dialysis. J Am Soc Nephrol. 2001 May;12(5):1046-1051. doi: 10.1681/ASN.V1251046.

  PMID: 11316864 BACKGROUND

• Davies SJ, Brown EA, Frandsen NE, Rodrigues AS, Rodriguez-Carmona A, Vychytil A, Macnamara E, Ekstrand A, Tranaeus A, Filho JC; EAPOS Group. Longitudinal membrane function in functionally anuric patients treated with APD: data from EAPOS on the effects of glucose and icodextrin prescription. Kidney Int. 2005 Apr;67(4):1609-15. doi: 10.1111/j.1523-1755.2005.00243.x.

  PMID: 15780118 BACKGROUND

• Balteau M, Tajeddine N, de Meester C, Ginion A, Des Rosiers C, Brady NR, Sommereyns C, Horman S, Vanoverschelde JL, Gailly P, Hue L, Bertrand L, Beauloye C. NADPH oxidase activation by hyperglycaemia in cardiomyocytes is independent of glucose metabolism but requires SGLT1. Cardiovasc Res. 2011 Nov 1;92(2):237-46. doi: 10.1093/cvr/cvr230. Epub 2011 Aug 22.

  PMID: 21859816 BACKGROUND

• Palazzo M, Gariboldi S, Zanobbio L, Selleri S, Dusio GF, Mauro V, Rossini A, Balsari A, Rumio C. Sodium-dependent glucose transporter-1 as a novel immunological player in the intestinal mucosa. J Immunol. 2008 Sep 1;181(5):3126-36. doi: 10.4049/jimmunol.181.5.3126.

  PMID: 18713983 BACKGROUND

• Schroppel B, Fischereder M, Wiese P, Segerer S, Huber S, Kretzler M, Heiss P, Sitter T, Schlondorff D. Expression of glucose transporters in human peritoneal mesothelial cells. Kidney Int. 1998 May;53(5):1278-87. doi: 10.1046/j.1523-1755.1998.00899.x.

  PMID: 9573543 BACKGROUND

• Fischereder M, Schroppel B, Wiese P, Fink M, Banas B, Schmidbauer S, Schlondorff D. Regulation of glucose transporters in human peritoneal mesothelial cells. J Nephrol. 2003 Jan-Feb;16(1):103-9.

  PMID: 12649541 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Biospecimens will be retained. Cells harvested from spent peritoneal dialysate will have RNA isolated and then cDNA will be preserved. Supernatent of spent peritoneal dialysate will be kept.

MeSH Terms

Conditions

Kidney Failure, Chronic; Peritoneal Fibrosis

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Peritoneal Diseases; Digestive System Diseases; Fibrosis

Study Officials

• Eric L Wallace, M.D.

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Target Duration: 3 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 30, 2014
• First Posted: May 8, 2014
• Study Start: May 1, 2014
• Primary Completion: March 1, 2017
• Study Completion: March 1, 2017
• Last Updated: April 19, 2017

Record last verified: 2017-04

Locations

US (1)